Concomitant Liver Disease Research Articles

MAFLD enhances clinical practice for liver disease in the Asia-Pacific region.

Fatty liver is now a major cause of liver disease in the Asia-Pacific region. Liver diseases in this region have distinctive characteristics. First, fatty liver is frequently observed in lean/normal-weight individuals. However, there is no standard definition of this unique phenotype. Second, fatty liver is often observed in patients with concomitant viral hepatitis. The exclusion of viral hepatitis from non-alcoholic fatty liver disease limits its value and detracts from the investigation and holistic management of coexisting fatty liver in patients with viral hepatitis. Third, fatty liver-associated hepatocellular carcinoma (HCC) is generally categorized as non-B non-C HCC. Fourth, the population is aging rapidly, and it is imperative to develop a practicable, low-intensity exercise program for elderly patients. Fifth, most patients and non-specialized healthcare professionals still lack an awareness of the significance of fatty liver both in terms of intrahepatic and extrahepatic disease and cancer. Recently, an international expert panel proposed a new definition of fatty liver: metabolic dysfunction-associated fatty liver disease (MAFLD). One feature of MAFLD is that metabolic dysfunction is a prerequisite for diagnosis. Pertinent to regional issues, MAFLD also provides its diagnostic criteria in lean/normal-weight individuals. Furthermore, MAFLD is independent of any concomitant liver disease, including viral hepatitis. Therefore, MAFLD may be a more suitable definition for fatty liver in the Asia-Pacific region. In this review, we introduce the regional characteristics of fatty liver and discuss the advantages of MAFLD for improving clinical practice for liver disease in the region.

The difference in prolonged continuous and intermittent Pringle maneuver during complex hepatectomy for hepatocellular carcinoma patients with chronic liver disease: A retrospective cohort study.

PurposeTo explore the differences between prolonged continuous Pringle maneuver (CPM) and prolonged intermittent Pringle maneuver (IPM) in patients with hepatocellular carcinoma (HCC), who underwent complex hepatectomy.MethodsThis retrospective cohort study performed between June 2014 and May 2016 included 142 patients who underwent complex hepatectomy for HCC and concomitant chronic liver disease but with good liver function. Patients were categorized into CPM (n = 69) and IPM groups (n = 73). The differences in these aspects were compared between the two groups which include operation time, intraoperative bleeding, perioperative transfusion, postoperative complications, liver function injury, postoperative overall survival (OS), and tumor recurrence.ResultsThe cumulative clamping time, operation time, intraoperative bleeding, and perioperative transfusion rates were 38.0, 132 min, 300 ml, and 17.4% in CPM and 40.0, 145 min, 400 ml, and 32.9% in IPM, respectively. There were significant intergroup differences in operation time (p = 0.018), intraoperative bleeding (p < 0.001), and perioperative transfusion rates (p = 0.034). Besides, the postoperative complications and postoperative liver function injury of the CPM group were better than those of IPM. There was no significant intergroup difference in OS (p = 0.908) and tumor recurrence (p = 0.671) between two groups.ConclusionCompared with IPM, CPM with a cumulative clamping time between 30 and 50 min can shorten operation time, reduce intraoperative bleeding and perioperative transfusion, and reduce postoperative complications and postoperative liver function injury in patients who underwent complex hepatectomy for HCC and concomitant liver disease but with good liver function. There was no significant difference in OS and tumor recurrence between two groups.

One liver, two samples and two diagnoses-An example of how multiple samples by laparoscopically guided liver biopsy can be decisive.

Laparoscopically-guided liver biopsy was performed to make the diagnosis in a 54-year old female patient with clinical and serological signs of both non-alcoholic fatty liver disease and autoimmune hepatitis (AIH). Figure A shows a sample from the right liver lobe (HE, 20x) with a blue-boxed area (Figure B) (HE, 100x) demonstrating a total of eight portal tracts. Macrovesicular steatosis of about 50% of hepatocytes and mild lymphocyte infiltration were detected.

S782 Increased Atherosclerotic Cardiovascular Disease and Heart Failure Risk in Inflammatory Bowel Disease Patients wWith Concomitant Non-Alcoholic Fatty Liver Disease: A Nationwide Analysis

S782 Increased Atherosclerotic Cardiovascular Disease and Heart Failure Risk in Inflammatory Bowel Disease Patients wWith Concomitant Non-Alcoholic Fatty Liver Disease: A Nationwide Analysis

Elevated liver enzymes of newly diagnosed pediatric celiac patients-a prospective-observational study.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p < 0.01) and more commonly presented with diarrhea (32.3% vs. 14.9%, p = 0.03). Eighty percent of patients with elevated ALT levels normalized their ALT within 3months and all within 1year. Following gluten-free diet initiation, patients with elevated ALT had similar clinical course, growth, serology normalization rate, and laboratory results, compared to patients with normal ALT over a 1-year follow-up. A single patient was simultaneously co-diagnosed with celiac disease and autoimmune hepatitis.Conclusion: Clinically significant ALT abnormalities are rare among newly diagnosed pediatric celiac patients. Significant elevations failing to normalize on a gluten-free diet should raise concern of a concomitant primary liver disease and warrant further investigations. What is Known: • Elevated liver enzymes may be an extra-intestinal manifestation of celiac disease. • Reported prevalences of ALT elevations among children with a new diagnosis of celiac disease ranges between 5 and 40%. What is New: • ALT elevations are present in 25% of children with a new diagnosis of celiac disease. • Significant elevations (>3 × ULN) are rare (1.6%). • Elevated liver enzymes are associated with earlier age at diagnosis. • The natural history of patients with elevated liver enzymes at diagnosis is comparable to those without.

Досвід застосування мінеральної води в лікуванні хворих на хронічний вірусний гепатит С із супутньою неалкогольною жировою хворобою печінки

У статті доведено доцільність внутрішнього курсового прийому мінеральної води (у подвоєному режимі дозування) у комплексному лікуванні хворих на хронічний вірусний гепатит С із супутньою неалкогольною жировою хворобою печінки з метою покращення клінічного перебігу основного та супутньо­го захворювань, відновлення функціонального стану печінки, зменшення інсулінорезистентності.

Оценка клинической эффективности заместительной терапии препаратом Декап у пациентов с сахарным диабетом типа 2 и сопутствующей неалкогольной жировой болезнью печени при дефиците витамина D

Актуальность. В последнее время дефицит витамина D считается одним из факторов развития сахарного диабета 2-го типа (СД типа 2) и неалкогольной жировой болезни печени (НАЖБП). Цель: установить эффективность препарата Декап (холекальциферол) у пациентов с его дефицитом, больных СД типа 2 с НАЖБП. Материалы и методы. Пролечены 52 пациента с НАЖБП и СД типа 2 на фоне установленного D-дефицита, которые были равномерно распределены на две группы. Больные группы сравнения (n = 26) получали исключительно традиционную антидиабетическую терапию, а больные основной группы (n = 26) дополнительно получали препарат витамина D Декап, который назначали в дозе 4000 МЕ/сут сроком на 6 месяцев. Результаты. Использование витамина D было ассоциировано со статистически значимым снижением гликемии натощак через 6 месяцев лечения на 4,2 % (p = 0,041). Уровень гликированного гемоглобина (HbA1c) в основной группе пациентов в среднем снизился на 0,38 % (р = 0,121) через 3 месяца и остался практически на том же уровне и через 6 месяцев — на 0,44 % (р = 0,088). Параллельно с улучшением параметров гликемического контроля у пациентов основной группы наблюдалась тенденция к снижению индекса HOMA-2-IR на 0,28 (–0,11; 0,86; р = 0,152) и улучшение чувствительности к инсулину на 1,39 (–10,04; 6,01; р = 0,621) по сравнению с исходным уровнем. Использование препарата витамина D (Декап) ассоциировано со снижением индексов стеатоза: FLI и TyG. Базовое значение для FLI составило 74,11 ± 18,71, для TyG — 5,21 ± 0,29, а после шестимесячного курса лечения витамином D снизилось соответственно на 4,4 % (р = 0,029) и 2,68 % (р = 0,031) по сравнению с исходными показателями. Выводы. Установлено, что использование препарата Декап у пациентов с дефицитом витамина D, больных СД типа 2 с НАЖХП, в дозе 4000 МЕ/сут на курс не менее шести месяцев приводит к улучшению параметров гликемического контроля и метаболического профиля.

Prevalence and Impact of Fatty Liver Disease in Adult Deceased Liver Transplant Donors: Metabolic-Associated Fatty Liver Disease or Nonalcoholic Fatty Liver Disease?

Donor hepatic steatosis is associated with worse post-liver transplant (LT) outcomes, especially when >30%(1). Such donors usually have non-alcoholic fatty liver disease (NAFLD) which is defined as fatty liver (hepatic steatosis >5%) without excessive alcohol consumption (>210g/week for men, >140g/week for women) or concomitant liver disease. Recently, international consensus have proposed that the term NAFLD be replaced by metabolic-associated liver disease (MAFLD)(2). New criteria define MAFLD as fatty liver together with the presence of metabolic conditions (i.e. type 2 diabetes mellitus, elevated ethnicity-specific body mass index (BMI), or at least two of: elevated waist circumference, hypertension, dyslipidemia, prediabetes, and/or insulin resistance)(2). We know these metabolic variables such as raised BMI and diabetes mellitus in a donor also contribute to graft marginality(1, 3). We examined whether a biopsy-proven diagnosis of NAFLD or MAFLD in a liver donor impacted on outcomes.

Chronic hepatitis B infection with concomitant hepatic steatosis: Current evidence and opinion.

With the increasing incidence of obesity and metabolic syndrome worldwide, concomitant nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has become highly prevalent. The risk of dual etiologies, outcome, and mechanism of CHB with concomitant NAFLD have not been fully characterized. In this review, we assessed the overlapping prevalence of metabolic disorders and CHB, assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD, and discussed the remaining clinical issues to be addressed in the outcome of such patients. We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation. For CHB patients, it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses. The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.

THE STATE OF PLATELET HEMOSTASIS IN PATIENTS WITH HYPERTENSIVE DISEASE COMBINED WITH NON-ALCOHOLIC FAT LIVER DISEASE

Relevance. Platelet activation and platelet aggregation are central processes in the pathophysiology of coronary heart disease and thrombosis. The relationship between cardiovascular morbidity and mortality varies with the presence of other concomitant cardiovascular risk factors.&#x0D; Objective. To determine the state of platelet hemostasis in patients with essential hypertension (HT), with concomitant non-alcoholic fatty liver disease (NAFLD).&#x0D; Materials and methods. 152 patients were examined: 72 men and 80 women. Three groups were identified: I - 46 patients with stage II HT without concomitant NAFLD, II - 54 patients with NAFLD without HT, group III - 52 patients with HT and concomitant NAFLD. A study of total platelet count, mean platelet volume (MPV), platelet distribution width (PDW), platelet count (PCT) and spontaneous platelet aggregation was performed.&#x0D; Results. The level of mean platelet volume (MPV) in both groups of patients with hepatic steatosis exceeded control values equally - by 6%, both in patients with NAFLD (p&lt;0.001) and in NAFLD with concomitant hypertension (p&lt;0.01). In patients of the NAFLD group and hypertension, the relative width of the platelet distribution by volume (PDW) had high values - 2% (p&lt;0.05) higher than in the control cohort, and 2.4% (p&lt;0.05) than in patients with isolated HT. An increase in the degree of spontaneous aggregation in patients of all surveyed groups compared to controls. So in patients with HT II stage. spontaneous aggregation increased 2.2 times (p&lt;0.001), while in both groups of patients with hepatic steatosis, the increase in spontaneous platelet activity was twice as high: in patients with NAFLD - 4.3 times (p&lt;0.001), in patients with HT II stage. and concomitant NAFLD - 4.1 times (p&lt;0.001).&#x0D; Conclusion. NAFLD is accompanied by an increased in MPV, the size of which correlates with their functional activity. In patients with isolated NAFLD, a statistically significant increase in spontaneous platelet aggregation is also observed, which allows considering NAFLD as one of the risk factors for thrombophilic changes in the primary hemostasis.

Saroglitazar for Nonalcoholic Fatty Liver Disease: A Single Centre Experience in 91 Patients

Saroglitazar is a novel, dual peroxisome proliferator-activated receptors-α/γ agonist and is being investigated for the treatment of nonalcoholic fatty liver disease (NAFLD). Consecutive overweight (body mass index [BMI] >23kg/m2) patients of NAFLD, diagnosed based on controlled attenuation parameter (CAP) >248dB/m, and attending the outpatient department of a tertiary care centre in New Delhi, were enrolled. Patients with cirrhosis (liver stiffness measurement[LSM] >13.5kPa) and those with concomitant liver disease due to other aetiologies (alcohol, viral, etc.) were excluded. All patients received saroglitazar 4mg/day; in addition, they were advised to reduce weight and were counselled regarding diet and exercise. At 3-month follow-up, patients were categorized into those who were able to reduce ≥5% body weight and those who could n'ot, and both these groups were compared. A total of 91 patients (median age 45 years [range 18-66years]; 81% men) were included in the study. The median BMI was 29.3kg/m2 (range 23.6-42.2kg/m2). The baseline median (range) aspartate transaminase, alanine transaminase, gamma glutamyl transferase, LSM and CAP values were 40IU/dL (range 22-144IU/dL), 48IU/dL (range 13-164IU/dL), 42IU/dL (range 4-171IU/dL), 6.7kPa (range 3.6-13.1kPa), and 308dB/m (range 249-400dB/m). All patients tolerated saroglitazar well. At 3-month, 57 patients (63%) were able to reduce ≥5% weight, whereas in the remaining 34 patients (37%), the weight reduction was <5% from baseline. Transaminases values improved in both the groups; however, LSM and CAP values improved only in patients who reduced weight. In overweight patients with NAFLD, a 3-month therapy with saroglitazar is able to improve transaminases but not LSM and CAP values unless accompanied by weight reduction of at least 5%. Larger randomized controlled trials are needed to document the independent effect of saroglitazar in these patients.

Occult hepatitis B infection in Turkish HIV-infected patients: A multicentre, retrospective, cross-sectional study, Schindler study.

Occult hepatitis B infection (OHBI) appears to have a higher prevalence in populations at high risk for hepatitis B virus (HBV) infection with concomitant liver disease. The aim was to assess the prevalence of OHBI in a sample of human immunodeficiency virus -1 positive and HBV surface antigen-negative (HIV-1+/HBsAg-) Turkish patients. Ten centres in Turkey were included in the study. Patients were selected on the basis of a power calculation with a known population size of HIV-positive patients and a reported prevalence of OHBI. Gender, age, occupation, place of residence, treatment and clinical status, and laboratory results, including immunodeficiency panel, antibody tests, hemogram, biochemistry, and coagulation studies were evaluated retrospectively. The number of HIV-infected patients followed in these centres was 3172 and the sample population numbered 278. All 278 were HBsAg negative. The mean age of the sample was 37.2±13.1years and 235 (84.5%) were male. All but one patient (99.6%) had been treated with antiretroviral therapy. Of the 278 patients, 169 (60.6%) were positive for Anti-HBs and 125 (44.8%) were positive for Anti-HBc IgG. HIV RNA was detected in 203/278 (73%) of the patients. Four HBV DNA (1.4%) were diagnosed with OHBI. There was no significant difference in hemogram, hemoglobin or bilirubin concentrations in those with OHBI compared with the other patients. In a representative sample of HIV+ patients from 10 Turkish centres, the prevalence of OHBI was found to be 1.4%. In HIV positive patients, it is important to identify those with OHBI for optimal clinical management and prognosis.

Individualized treatment options for patients with non-cirrhotic and cirrhotic liver disease.

The obesity pandemic has led to a significant increase in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). While dyslipidemia, type 2 diabetes mellitus and cardiovascular diseases guide treatment in patients without signs of liver fibrosis, liver related morbidity and mortality becomes relevant for MAFLD’s progressive form, non-alcoholic steatohepatitis (NASH), and upon development of liver fibrosis. Statins should be prescribed in patients without significant fibrosis despite concomitant liver diseases but are underutilized in the real-world setting. Bariatric surgery, especially Y-Roux bypass, has been proven to be superior to conservative and/or medical treatment for weight loss and resolution of obesity-associated diseases, but comes at a low but existent risk of surgical complications, reoperations and very rarely, paradoxical progression of NASH. Once end-stage liver disease develops, obese patients benefit from liver transplantation (LT), but may be at increased risk of perioperative infectious complications. After LT, metabolic comorbidities are commonly observed, irrespective of the underlying liver disease, but MAFLD/NASH patients are at even higher risk of disease recurrence. Few studies with low patient numbers evaluated if, and when, bariatric surgery may be an option to avoid disease recurrence but more high-quality studies are needed to establish clear recommendations. In this review, we summarize the most recent literature on treatment options for MAFLD and NASH and highlight important considerations to tailor therapy to individual patient’s needs in light of their risk profile.

COLORECTAL ADENOCARCINOMA DEVELOPING IN A YOUNG FEMALE WITH OVERLAP SYNDROME AND VERY EARLY ONSET-INFLAMMATORY BOWEL DISEASE: A CASE REPORT

Abstract We present a 4-year-old female diagnosed with very-early onset inflammatory bowel disease (VEO-IBD), ulcerative colitis type, and overlap syndrome based on clinical presentation, blood and stool studies, diagnostic endoscopies and liver biopsy. Her clinical course was complicated by pervasive psychological stressors, non-compliance with medical therapy, and frequent provider changes. Initial treatment included Prednisone, 6-mercaptopurine and Ursodiol. Treatment was escalated to include multiple biological agents which were stopped prematurely due to non-adherence. She developed weight loss and growth stunting, necessitating exclusive enteral nutrition and then parenteral nutrition. Due to medically refractory disease, she underwent a total colectomy with end ileostomy at the age of 13. Pathology revealed stage III colorectal adenocarcinoma (CRC) with lymph node involvement and transmural inflammation diagnostic of Crohn’s disease (CD). Genetic testing of the resected colon noted a missense mutation of TP53. Our patient completed 6 cycles of extensive and targeted chemotherapy with no evidence of disease reccurrence. She recently underwent ileal pouch-anal anastomosis and creation of a diverting ileostomy. CRC is exceedingly rare in pediatric IBD (PIBD) patients, with less than 30 reported cases in the available literature1. Most cases occurred in males and patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC), where the risk of developing CRC is four times greater2. The risk of CRC increases with disease duration, with most PIBD patients developing CRC at 25 years of age1. Interestingly, mutations in TP53, a tumour suppressor gene, have been found to occur more frequently in patients with IBD-CRC compared to those with sporadic-CRC or IBD without dysplasia3. Mutations in TP53 may not only increase a patients general susceptibility to CRC but may also accelerate its development by contributing to excessive inflammation4. Our patient’s treatment refractory clinical course and transition in IBD diagnosis from UC to CD highlights the complexity of VEO-IBD management. While rare in pediatric patients, the development of CRC is a life-threatening risk and it should be considered in patients with prolonged and severely refractory IBD with concomitant autoimmune liver disease. Our patient’s young age at the time of CRC diagnosis emphasizes the need for vigilant yearly endoscopic screening and development of pediatric guidelines for dysplasia monitoring in this high risk population. Further research is needed to evaluate the role of genetic variant screening in CRC risk stratification.

COVID-19 AND PRIMARY CARE: POSSIBILITIES FOR INCREASING POSITIVE OUTCOMES

The aim: Determine the most common non-communicable diseases which are associated with an increased rate of moderate and severe COVID-19 infection. Identify the best tools for diagnosing COVID-19 and predicting the deterioration of the disease. Materials and methods: Publications were processed and analyzed according to the keywords of the topic of work “COVID-19”, “non-communicable disease”, “obesity”, “hypertension”, “Comorbidities”, “frailty”, “diabetes”, “chronic obstructive pulmonary disease”, “cardio-vascular diseases”, “liver diseases”, “diagnostic tools”, “outcomes” in the databases of PubMed, MEDLINE, Web of Science. Conclusions: As a result of the analysis, we found that patients with concomitant obesity, diabetes mellitus, COPD, CVD and liver diseases have an increased the risk of severe forms and death from COVID-19.

MAFLD AND NAFLD: is there the need for redefining the risk of cardiovascular disease and mortality?

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is characterized by a high burden of metabolic alterations. It exposes patients to increased morbidity and mortality, mostly driven by cardiovascular (CV) complications. Despite its large use, the nomenclature NAFLD has some limitations, due to the exclusion of patients with hepatic fat and concomitant other liver diseases or moderate alcohol consumption possibly contributing to hepatic damage. Therefore, a new and more inclusive definition of fatty liver has recently been proposed, namely metabolic associated fatty liver disease (MAFLD). It comprises patients with hepatic steatosis and associated metabolic comorbidities, without exclusion of other liver diseases. As for the nature of the new definition of MAFLD, it could be speculated that an increased risk of cardiovascular complications should be expected. Therefore, our review aims at answering the question about possible differences in cardiovascular risk and mortality in patients with NAFLD compared to MAFLD. We selected 8 studies out of 1130 by searching in the PubMed database. Data from literature seem to report an increased risk of CV events and mortality in patients affected by MAFLD compared to NAFLD, possibly due to the metabolic burden and coexistence of other liver diseases typical of MAFLD. However, further prospective studies are warranted to confirm this preliminary hypothesis.

PNPLA3 rs738409 polymorphism in Patients with Type 2 Diabetes and Concomitant Liver Pathology in Yakutia

Background: The pathogenetic mechanisms of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) are closely related. Currently, multiple studies have demonstrated a link between the PNPLA3 148M variant and the development and progression of NAFLD, including liver fibrosis. The aim of our research was to study the distribution of alleles and genotypes of the PNPLA3 rs738409 SNP in Russians and Yakuts living in Yakutia, as well as to search for associations of the PNPLA3 rs738409 SNP in patients with T2D and non-alcoholic fatty liver disease / non-alcoholic steatohepatitis. Methods and Results: The study included 179 patients (28 Russians and 151 Yakuts) with T2D and concomitant liver diseases of non-infectious origin. The comparison group consisted of 147 healthy volunteers of Russian ethnicity and 246 healthy volunteers of Yakut ethnicity. The PNPLA3 738409 SNP was analyzed by PCR-RFLP reaction. The results found a significant difference between the frequencies of the PNPLA3 rs738409 genotypes and alleles in Russians and Yakuts, both among healthy volunteers and in T2D patients with liver diseases. The frequency of the G allele occurrence in the group of healthy Yakuts was significantly higher (OR- 3.313; 95% CI: 2.444-4.499; P&lt;0.001) than in the group of healthy Russians. No significant differences were found for the PNPLA3 rs738409 genotype and allele frequencies among a healthy sample and a sample of T2D patients with non-alcoholic fatty liver disease / non-alcoholic steatohepatitis, both in the Russian and Yakut populations.

Clinical and experimental substantiation of the use of bentonite suspension in the complex rehabilitation of patients with chronic viral hepatitis C with concomitant non-alcoholic fatty liver disease

Introduction. One of the most severe diffuse liver diseases is chronic viral hepatitis C (CHC) combined with non-alcoholic fatty liver disease (NAFLD). After completing the treatment of CHC with drugs of direct antiviral action, there remains a high risk of further progression of liver fibrosis associated with the presence of comorbid pathology - NAFLD in patients. The above circumstances initiated us to search for new non-drug technologies to treat this category of patients. Purpose of the work: to study the effectiveness of use bentonite suspension in rats with a model of NAFLD and to substantiate the practicality of using bentonite in the complex treatment of CHC patients with concomitant NAFLD. Methods: experimental, anamnestic and clinical, general clinical, biochemical, determination of the HOMA index, leptin and adiponectin levels, ultrasonographic studies of the digestive system, bacteriological examination of feces, statistical methods.Results: According to microscopic examination, bentonite application in animals with the NAFLC model leads to a decrease in liver steatosis, restoration of bile formation and bile secretion, and protein-synthesizing liver function. In the blood, there was a positive dynamics to the restoration of energy-dependent transmembrane ion transport according to the activity of Na+/K+ -ATPase and Mg2+/Ca2+ -ATPase (in the liver tissue) and the balance of the antioxidant system (to restrain malondialdehyde and catalase activity). We examined 40 patients with CHC with concomitant NAFLD, who completed the course of antiviral therapy (AVT) and were divided into two groups. 1 (control) group (20 people) received a basic treatment complex (diet therapy, which corresponded to the Mediterranean diet, a regimen of dosed physical exertion, patients of 2 groups (20 people, the main group) additionally received a preparation based on bentonite clay inside - 10 days (1 dose three times a day) Evaluation of the effectiveness of treatment was carried out one month after the start of treatment. Conclusion: The treatment carried out in both groups was accompanied by positive dynamics in most of the diseaseʹs symptoms. But a significant advantage was observed in the second group, where the normalization of cholestatic and dyslipidemic syndromes was established, that is, the effect on the pathogenetic links of the progression of NAFLD was proved. The results obtained confirm the practicality of using the drug with bentonite in the complex treatment of CHC patients with concomitant NAFLD. Keywords: chronic viral hepatitis C, non-alcoholic fatty liver disease, bentonite clay,

THE RS1801282 PPARG POLYMORPHISM DEPENDENT METABOLIC EFFECTS OF PIOGLITAZONE IN PATIENTS WITH OBESITY AND CONCOMITANT NAFLD

The aim: to investigate the metabolic effects of different treatment options in patients with obesity and concomitant non-alcoholic fatty liver disease (NAFLD) based on the presence of CG and GG genotypes PPARG rs1801282 (Pro12Ala) polymorphism in Ukrainians. Materials and methods: 123 patients with NAFLD in combination with obesity 1, 2, 3 classes were included in the motivational weight loss program (5 visits, 3 months). The case group was treated with pioglitazone 15 mg / day, while the control group received only a program. Ultrasound steatometry, anthropometric and laboratory tests before and after treatment, genetic testing rs1801282 polymorphism in PPARG gene were performed. Results: the carriers of CG and GG genotypes PPARG rs1801282 polymorphism had less high stimulated insulin levels compared with groups of different genotypes (p&lt;0.001). It was found pioglitazone effectiveness with significant difference in dynamics of CAP reduction (p&lt;0.001) regardless of polymorphism. Dynamics of BMI decrease was the lowest in control group CC carries – –2.81 (–3.23; –2.39) kg (p&lt;0.001) compared among other groups. Subjects from pioglitazone group with rs1801282 polymorphism carrying of CG and GG genotypes had significant differences in dynamics of fasting С-peptide decrease, serum uric acid reduction – –1.31 (–1.50; –1.13) µg/L and -165.3 (–182.80; –147.80) µmol/L (p&lt;0.001) respectively compared among other groups. Conclusions: Better reduction of metabolic parameters during pioglitazone treatment of patients with obesity and concomitant NAFLD appears to be associated with carrying of CG and GG genotypes PPARG rs1801282 polymorphism.

Impact of liver disease on oral anticoagulant prescription and major adverse events in patients with atrial fibrillation: analysis from a population-based cohort study

Abstract Aims Data on the impact of liver disease (LD) in patients with atrial fibrillation (AF) and the role of oral anticoagulant (OAC) drugs for stroke prevention, are limited. We analysed the impact of LD and OAC treatment in determining stroke, major bleeding, all-cause death and secondary bleeding outcomes. Methods A retrospective observational population-based cohort study. The study cohort is derived from the administrative health databases of Lombardy region (&amp;gt;10 million inhabitants), Italy. All AF patients ≥40 years admitted to hospital from 2000 to 2018 were considered. AF and LD diagnosis were established using ICD9-CM codes. Use of OAC was determined with Anatomical Therapeutic Chemical (ATC) codes. Primary study outcomes were stroke, major bleeding and all-cause death. Results Among 393,507 AF patients, 16,168 (4.1%) had concomitant LD. LD AF patients were significantly less treated with OAC independent of associated clinical characteristics (OR: 0.96, 95% CI: 0.92–0.98). Concomitant LD was found associated with an increased risk in all the study outcomes (HR: 1.18, 95% CI: 1.11–1.25 for stroke; HR: 1.57, 95% CI: 1.47–1.66 for major bleeding; HR: 1.41, 95% CI: 1.39–1.44 for all-cause death. Use of OAC in patients with AF and LD resulted in a reduction in stroke (HR: 0.80, 95% CI: 0.70–0.92), major bleeding (HR: 0.86, 95% CI: 0.74–0.99) and all-cause death (HR: 0.85, 95% CI: 0.80–0.90), with similar results according to several clinically relevant subgroups. A net clinical benefit (NCB) analysis suggested a positive benefit/risk ratio in using OAC in AF patients with LD (NCB: 0.408, 95% CI: 0.375–0.472). Conclusions In AF patients, concomitant LD carries a significantly higher risk for all clinical outcomes. Use of OAC in AF patients with LD was associated with a significant benefit/risk ratio, even in high-risk patient subgroups. Funding Acknowledgement Type of funding source: None